Arachidonic acid metabolism in glutathione-deficient macrophages.
Mouse resident peritoneal macrophages were treated with the glutathione (GSH) synthesis inhibitor buthionine sulfoximine to deplete intracellular GSH. The arachidonic acid metabolites released by the GSH-depleted macrophages in response to a zymosan challenge were analyzed by HPLC. Buthionine sulfoximine treatment resulted in inhibition of both prostaglandin E2 and leukotriene C synthesis that was directly related to the degree of GSH depletion. Macrophages in which GSH levels were reduced to 3% of normal exhibited reductions to 4% and 1%, respectively, in PGE2 and LTC formation. The total quantity of cyclooxygenase metabolites secreted by GSH-deficient macrophages was identical to that of control cells as a result of increased synthesis of prostacyclin and, to a lesser extent, 12-L-hydroxy-5,8,10-heptadecatrienoic acid. Total lipoxygenase products were decreased, however; increased formation of hydroxyicosatetraenoic acids only partially compensated for the deficit in leukotriene C production. These findings extent our earlier observations on the inhibition of leukotriene C synthesis in GSH-depleted macrophages and confirm with intact cells the previously suggested role of GSH in prostaglandin E2 formation.
D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D002470:Cell Survival; D011464:Epoprostenol / Q000096:biosynthesis*; D005978:Glutathione / Q000172:deficiency*; D008264:Macrophages / Q000378:metabolism*; D010587:Phagocytosis; D011453:Prostaglandins / Q000096:biosynthesis*; D011458:Prostaglandins E / Q000096:biosynthesis*; D015054:Zymosan
D001095:Arachidonic Acids; D011453:Prostaglandins; D011458:Prostaglandins E; D016718:Arachidonic Acid; D015054:Zymosan; D011464:Epoprostenol; D005978:Glutathione